Abstract The epidermis is an important site of the im- munoinflammatory response in the skin. In the present study, the expression of cytokine and ICAM-1 (intercellu- lar adhesion molecule-1) genes was evaluated by RT-PCR in the epidermis isolated from biopsies from 25 reactional leprosy patients. TNFα and IL-6 mRNAs were detected in all individuals during the reactional state (reversal reac- tion or erythema nodosum leprosum), IL-8 message was detected in 66.6% and 62.5% of the patients, IL-12 mRNA was present in 91.6% and 62.5% and ICAM-1 in 100% and 71.4%, respectively. In addition, when skin biopsies were obtained from the same patients before and during the reactional episode, an enhancement in cytokine mRNA, but not in ICAM-1 mRNA, was observed. Seven patients were also evaluated at the onset of reaction and during antiinflammatory treatment. In contrast to a preferential decrease in the TNFα gene detected in the dermis, during the treatment phase, persistent/enhanced TNFα mRNA expression was detected in the epidermis in six out of the seven patients assessed. This peculiar pattern of expres- sion might reflect a differential impact that in vivo anti- inflammatory therapy has on the epidermis. The present findings indicate that the epidermis plays an important role in the local inflammatory response in leprosy and that the profile of response detected in the epidermis during the reactions may be regulated differently from that in the dermis. Keywords TNFα · ICAM-1 · Leprosy · Epidermis Introduction The skin is an important component of the immune sys- tem (skin immune system, SIS) responding to a diverse range of stimuli. Perturbation of the skin barrier is ob- served in several inflammatory diseases such as dermati- tis, eczema and psoriasis, and in most cases, it is the basis for the immediate innate response and inflammation ob- served in situ (Nickoloff 1999). Analysis of cytokine mRNA expression by RT-PCR has shown a differentiated profile between normal and inflamed epidermis in that the ex- pression of proinflammatory cytokines, such as inter- leukin-1β (IL-1β), IL-6, IL-8, IL-12, and tumor necrosis factor-α (TNFα), is enhanced in the epidermis as well as in the dermis (Nickoloff and Naidu 1994). In leprosy, accumulated evidence points to an altered histological pattern in the dermis and epidermis in both clinical forms (lepromatous and tuberculoid) and during the reactional states (reversal reaction, RR, and erythema nodosum leprosum, ENL). Reactions in leprosy represent acute states of inflammatory and immune response against the bacteria that may occur in the course of the chronic disease. The presence of an inflammatory infil- trate with predominance of CD4 + T cells, differentiated macrophages and thickened epidermis has been observed in reactional lesions and in the tuberculoid form which is characterized by the presence of a cell-mediated immune (CMI) response, few skin lesions and the absence of bac- teria, as opposed to the lepromatous form which is char- acterized by the absence of CMI, high bacterial load and several skin lesions and in which a flattened epidermis, absence of granuloma formation and preponderance of CD8 + T cells are found in situ (Van Voorhis et al. 1982). There is increasing evidence that, in addition to the dermis, the epidermis is the site of intense immunological reactivity during the reactions. An immunohistological study of lepromin biopsies has shown significant changes in the epidermis (Dugan et al. 1985). Most noteworthy is an increase in epidermal thickness with more than 90% of the basal keratinocytes expressing HLA-DR, an increase Rosane M. B. Teles · Milton O. Moraes · Natasha T. R. Geraldo · Ana M. Salles · Euzenir N. Sarno · Elizabeth P. Sampaio Differential TNFα mRNA regulation detected in the epidermis of leprosy patients Arch Dermatol Res (2002) 294 : 355–362 DOI 10.1007/s00403-002-0340-0 Received: 21 September 2001 / Revised: 24 April 2002 / Accepted: 31 July 2002 / Published online: 26 September 2002 ORIGINAL PAPER R.M.B. Teles · M.O. Moraes · N.T.R. Geraldo · A.M. Salles · E.N. Sarno · E.P. Sampaio (✉) Leprosy Laboratory, Oswaldo Cruz Institute, Fiocruz, Av. Brasil 4365, Manguinhos, Cep 21.045-900, Rio de Janeiro, Brazil e-mail: esampaio@gene.dbbm.fiocruz.br, Fax: +55-21-2709997 © Springer-Verlag 2002